Farmers in the South started noticing the problem before anyone else. When they sprayed their fields with Roundup weed killer, weeds kept growing anyway. In some areas, fields became so choked with weeds that farmers abandoned them.

Midwestern farmers have been watching the troubles in the South. Roundup, or its ingredient, glyphosate, is used with crops genetically modified to withstand the herbicide and has become the most ubiquitous product in American farming. It has meant less pesticide use. Less environmentally damaging tillage. And it has helped catapult Creve Coeur-based Monsanto, the developer of the Roundup Ready system, into the most dominant player in the seed industry.

But now, this silver bullet of American agriculture is beginning to miss its mark. The herbicide-resistant weeds that have plagued Southern farmers are emerging in Missouri with similar tenacity.

"It's a serious, serious problem," said Blake Hurst, a corn and soy farmer in northwestern Missouri and vice president of the board of the Missouri Farm Bureau. "The further north you get, the less of a problem it's been so far. Farmers here are denying it's going to happen to them. But guess what? It's on the way to your farm."

So far, glyphosate-resistant weeds have been found in at least 22 states. Last month, University of Missouri researchers confirmed that herbicide resistant giant ragweed has been found on 12 farms, bringing the total count of herbicide-resistant weeds in the state to five.

"There is no question glyphosate is a once-in-a-century herbicide," said Kevin Bradley, a weed scientist with the University of Missouri who conducted the giant ragweed survey. "The problem is that glyphosate has been so good that farmers have gotten spoiled a little bit ... We can't continue to abuse the system, which is just using Roundup Ready soybeans and spraying glyphosate over and over and over."

Monsanto, and the farmers who use its products, stress that glyphosate is still an effective product, one that controls more than 300 weeds. But the company acknowledges that it may have underestimated how long it would take for weeds to become resistant to the chemical and that it should have educated farmers sooner about the issue.

"With the benefit of hindsight, we could have been more aggressive with education," said John Combest, a Monsanto spokesman. "In the industry, we could've used more talk about diversity and multiple modes of action."

But, many farmers point out, that the efficacy of the Roundup system made it tempting to be lulled into complacency. "Glyphosate is clearly the cheapest weed control there is, and that's part of the problem," Hurst said. "It's easy."

Monsanto and other biotech industry players have been working with university extensions and farm groups to urge farmers to use different herbicides that work in different ways. Monsanto is even offering subsidies to Southern farmers - of about $12 an acre - as an incentive to use other companies' products to keep Roundup viable. The company also recently announced the launch of a new herbicide, Warrant, which can be used on cotton and soybeans and has been effective in some areas.

Meanwhile, the biggest drag on Monsanto's profitability has been the decline in its Roundup business. In the last quarter, Monsanto's Roundup and glyphosate business fell 56 percent. The reason: a flood of Chinese-made generic weed killer saturating the U.S. market that forced Monsanto to slash prices.

"There have been multiple Chinese manufacturers of glyphosate, so there's been a lot of surplus, and that's putting pressure on profits," said Jeff Windau, of Edward Jones & Co. "Now, in addition to that, we've got this ‘superweed' problem."

For farmers, herbicide resistance means more work and more money spent on different products and approaches.

"We're spraying more," Hurst said. "The key is to rotate chemicals and completely different modes of action, and we're probably going to have to go back to older chemicals."

One of the benefits of the Roundup Ready system farmers point out, is that it has meant less erosion-inducing tillage, or plowing under of weeds. "It allows us to save soil," Hurst said.

Now farmers are resorting to tilling and environmentally damaging chemicals they haven't used in decades. The success of Roundup has left few options.

"It's led us down a narrow path," said Rick Oswald, president of the Missouri Farmers Union. "Most of the chemical companies quit developing other herbicides, so all there is Roundup or something that was around 20 years ago."

Some farmers say they are turning to conventional varieties of herbicides because they are unwilling to pay a higher price for a Roundup system that isn't working as it once did. But some younger farmers have never farmed any other way.

"They only know glyphosate," Hurst said. "But we're going to have to be better than this. It's going to take a lot better management, that's for sure."